High-risk Coronary Patients Research Articles

Changes in Sample Size and Length of Follow-up to Maintain Power in The Coronary Artery Bypass Graft (CABG) Patch Trial

The CABG Patch Trial is testing the hypothesis that prophylactic use of implantable cardiac defibrillators (ICDs) will improve survival in high-risk coronary heart disease patients undergoing CABG surgery. The original design called for 800 patients to be randomized to ICD prophylaxis or to no therapy and followed for 2 to 6.5 years (average, 40 months) to a common termination date. Since the ICD pulse generators used in this trial lasted about 42 months, the original design required ICD replacement in many patients. At its first two meetings in 1993, the Data and Safety Monitoring Board (DSMB) formalized a plan to adjust sample size in October 1994 if the control group mortality rate was lower than expected. In June 1994, an unanticipated and unique event—a subpoena from the Office of the Inspector General (OIG)—made it impossible to replace about half of the ICD generators and threatened to shorten follow-up substantially. If follow-up had been stopped on the date originally planned, but without replacing ICDs, the average follow-up would have fallen from 40 months to about 33 months. Also, in October 1994, the control group mortality rate was found to be somewhat lower than expected. Together, the abbreviated follow-up and lower control group mortality threatened to reduce power substantially. The DSMB reviewed several options for restoring power. Because mortality rates in the first month after CABG surgery were about seven times as high as thereafter and because ICD therapy did not reduce surgical mortality (death during the first 30 days), extending the follow-up benefits power more than does increasing the sample size. However, the limit on extending follow-up was 42 months (the expected battery life of the ICD). Data from the ICD-treated group was not reviewed or considered in making the decision. After reviewing many options for restoring power, the DSMB recommended that the sample size be increased from 800 to 900 patients and that almost all patients be followed for 42 months. This recommendation extended follow-up for 2 years beyond the original termination date planned for the trial and dictated that patients close out after 42 months rather than on a common termination date.

Cost-Effective Management of High-Risk Patients: A Case-Map Approach

Background. The case-management approach to patient care used by most cardiac surgical practices frequently highlights patients designated as high-risk. Increased risk might be because of advanced age, the need for complex reoperations, high risk of bleeding, and renal failure, all of which may be superimposed on poor ventricular performance. Methods. A small consensus panel of cardiac surgeons, anesthesiologists, perfusionists, cardiac-care nurse managers, and coagulation experts met to assess the potential for development of case-management pathways targeted towards high-risk coronary artery bypass graft patients. The process comprised review of the literature to identify risk factors and strategies most cost-effective in reducing risk. Results. A series of management strategies driven by data from the literature—or by consensus when such information was not available—were developed to cost-effectively manage the high-risk patient. The process was then converted to a multidimensional computer program. This personal computer-driven program served as a framework upon which any institution could impose its own practice style and modify recommendations. The program was designed to be interactive and to allow easy transition from patient-management strategies to support data. A facilitator generally coordinates the interaction between the local patient-care group and the computer information base to evolve a case-management map. Conclusions. By using stored information based on current literature and easily updated, the system is both educational and product oriented, and provides a case-map approach to the cost-effective management of patients during the preoperative, intraoperative, and postoperative phases of hospital care.

Background, Outcome, and Clinical Implications of the Multicenter Automatic Defibrillator Implantation Trial (MADIT)

Malignant ventricular tachyarrhythmias account for approximately one half of the estimated 1,000,000 people who die from cardiac causes annually. In 1990, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) group of investigators set out to determine if an implanted cardioverter defibrillator (ICD) would improve survival in patients with coronary disease at high risk for ventricular arrhythmias. The recently reported results from the MADIT study indicate that the ICD does save lives in high-risk coronary patients with left ventricular dysfunction and nonsustained ventricular tachycardia.[1]

Update on MADIT: The multkenter automatic defibrillator implantation trial

I n 1990, we developed the Multicenter Automatic Defibrillator Implantation Trial (MADIT) hypothesis, that an implanted cardioverter-defibrillator (ICD) would improve survival in high-risk coronary patients when compared with conventional medical management. In the subsequent trial we did not prespecify a comparison drug; management in the conventional arm was left to the discretion of the attending cardiologist, provided the drug was FDA approved. There were 32 participating centers, 30 in the United States and 2 in EuroDe. We enrolled the first patient into MADIT on Didember 27, 1990. The safety monitoring committee recommended termination of the trial on March 2 1, 1996, and the investigators and executive committee met on March 24, 1996, and agreed to terminate the trial. By that time we had randomized 196 patients. The average duration of follow-up was 27 months. The endpoint of this study was total mortality; there were 54 deaths at the time the trial was stopped. Patient enrollment Gteria were nonsustained ventricular tachycardia, prior Q-wave infarction, ejection fraction <35%, and electrophysiologic induction of ventricular tachycardia nonsuppressible with intravenous, procainamide. Thus, all subjects were at high risk. Average ejection fraction turned out to be 26% and the average age was 67 years. Randomization into defibrillator versus best conventional treatment arms tias well balanced. The major dmg used in the nondevice arm (74% of patients) was amiodarone. There were very few patients on type IA agents and none on type IC (Table I). The Kaplan-Meier camulative survival curve for the 196 patients after randomization showed im-

Assessment of coronary artery bypass graft surgery performance in New York. Is there a bias against taking high-risk patients?

The purpose of this study was to determine whether performing coronary artery bypass surgery on high-risk patients adversely affects the risk-adjusted mortality rates for patients of surgeons and hospitals in New York State compared with the impact of performing surgery on more routine patients. Risk-adjusted mortality-rates were calculated for 31 hospitals and 87 surgeons for high-risk (a predicted mortality rate of at least 7.5%) and low-risk patients during the time period 1990 to 1992. The risk-adjusted mortality for all high-risk patients was lower (2.94%) than the risk-adjusted mortality for other patients (3.02%). Fifteen of the 31 hospitals had a lower risk-adjusted mortality for all patients than they did for low-risk patients only, and no differences in either direction were statistically significant. Forty-one of 87 surgeons (47%) had risk-adjusted mortality for all patients that was at least as low as the risk-adjusted mortality for low-risk patients. In general, hospitals and surgeons with the lowest risk-adjusted mortality for all cases also had the lowest risk-adjusted mortality for high-risk cases. The authors conclude that there is no systematic bias against operating on high-risk coronary artery bypass graft patients in the risk-adjusted performance system in New York.

Aspirin and Other Platelet-Active Drugs: The Relationship Among Dose, Effectiveness, and Side Effects

Aspirin and Other Platelet-Active Drugs: The Relationship Among Dose, Effectiveness, and Side Effects

Cardiopulmonary bypass support of high risk coronary angioplasty patients: registry results.

Coronary angioplasty has been increasingly utilized in patients with extensive coronary disease, severe and acute chest pain syndromes, and poor ventricular function. This process has been facilitated in part by use of circulatory support, including perfusion balloons, intraaortic balloon pumps and cardiopulmonary bypass support systems. Percutaneous cannulation has facilitated elective and emergency application of cardiopulmonary bypass support in patients undergoing high risk coronary angioplasty. A National Registry of 25 centers has accumulated data on 801 elective and 210 emergency support angioplasty patients. Standby cardiopulmonary bypass support of elective high risk patients was associated with fewer complications and less in-hospital mortality in patients other than those with left ventricular ejection fraction < or = 20% and possibly older high risk patients. In elective cases, circulatory support was required in only approximately 7% of high risk patients, although need appeared to be unpredictable. Emergency use of cardiopulmonary bypass support, initiated < 20 minutes from the time of circulatory collapse, was associated with improved patient prognosis. Overall, patients undergoing circulatory cardiopulmonary bypass supported angioplasty had a marked reduction in anginal status, improvement in left ventricular ejection fraction and good (80%) 2-year survival. Although used only occasionally, circulatory support remains an important prophylactic interventional tool for the extremely high risk patient (left ventricular ejection fraction < or = 20%) and a lifesaving emergency technique for the occasional patient with circulatory collapse.

Role of Percutaneous Cardiopulmonary Bypass and Other Support Devices in Interventional Cardiology

Percutaneous cardiopulmonary bypass support has a role to play in the management of the high-risk coronary angioplasty patient. This article discusses the basic principles of cardiopulmonary bypass, technique, indications, and complications of this new addition to interventional cardiology. In addition, the role of other support devices during high-risk coronary interventions is also discussed.

Percutaneous Cardiopulmonary Support in High-risk Angioplasty

Percutaneous femoro-femoral cardiopulmonary bypass, cardiopulmonary support (CPS), has a role to play in the management of the high-risk coronary angioplasty patient. This article discusses the basic principles of cardiopulmonary bypass, technique, indications, complications, and future directions of this new addition to interventional cardiology.

Low and high risk coronary patients discriminated by blood platelet fatty acid composition.

The distribution of 11 long-chain fatty acids in platelet phospholipids were subjected to multivariate statistical analysis with groups of high and low risk coronary patients and controls. The alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had significant explanatory power between the groups. As has been anticipated from studies in Eskimos, the EPA fraction was low in coronary patients. It was lower in high risk patients than in low risk patients, and lower in patients below rather than above, 60 years of age. Young high risk patients had 1.2 +/- 0.2% (Mean, SE) EPA against 1.8 +/- 0.2% in young controls, (p = 0.035). Old low risk patients had the highest EPA and also the highest DHA, 2.9 +/- 0.3% against 2.3 +/- 0.2% in controls. The ALA was low in low risk patients. Patients with low platelet EPA and high serum cholesterol should be included in trials with EPA rich diets.

Warm induction of cardioplegia with glutamate-enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon support: Initial experience and operative strategy

This report reviews the initial clinical application of our experimental studies inducing cardioplegia with a warm (37 degrees C) glutamate-enriched blood solution in ischemically damaged hearts. Over 15 months, 23 consecutive coronary patients requiring preoperative intra-aortic balloon and inotropic drug support for cardiogenic shock underwent operation for left ventricular power failure. Twelve patients were given a warm glutamate-enriched blood cardioplegic solution during the first 5 minutes of aortic clamping before multidose cold (4 degrees C) glutamate blood cardioplegia was begun; 11 patients received standard multidose cold blood cardioplegia without glutamate. All patients had comparably depressed left ventricular performance preoperatively despite maximal inotropic and balloon support and showed evidence of extending myocardial infarction. They did not differ in the number of grafts placed (3.7 +/- 0.2), associated valve and aneurysm procedures (seven patients) or cross-clamp time (89 +/- 6 minutes). All patients received warm blood cardioplegic reperfusion before aortic unclamping. The perioperative mortality was 9% (2/23); both patients who died received cold blood cardioplegia without glutamate. In addition to lower mortality, patients receiving warm glutamate blood cardioplegia exhibited better hemodynamics, allowing earlier discontinuation of inotropic drug infusion (1.3 +/- 0.5 versus 2.7 +/- 0.8 days, p less than 0.05) and intraaortic balloon support (1.2 +/- 0.2 versus 3.6 +/- 0.5 days, p less than 0.05). Late mortality was 30%, resulting in a 65% overall survival rate (2 to 15 months) for the entire series of patients. The operative principles evolving from this early experience include (1) warm blood cardioplegic induction, (2) glutamate enrichment, (3) meticulous attention to cardioplegic distribution and grafting sequence, (4) warm cardioplegic reperfusion before unclamping, and (5) graft perfusion during construction of proximal anastomoses. Hopefully, further application of these techniques will improve results in these extremely high risk coronary patients requiring operation.

Therapeutic implications of myocardial lactate metabolism in patients considered candidates for emergency myocardial revascularization

Cardiac angiography has had limited success in predicting the potential for salvage of jeopardized ischemic myocardium. In this context, we have examined the effect of coronary sinus pacing on myocardial lactate extraction in order to determine its predictive role. All 159 patients with unstable angina or acute myocardial infarction were found angiographically suited for coronary bypass surgery. In addition, myocardial lactate extraction was assessed prior to, during, and after coronary sinus pacing. Conventional medical treatment was carried out in 72 patients, whereas 87 patients were treated with coronary bypass surgery. Therapy was determined on clinical and angiographic grounds, independent of myocardial lactate extraction. In medically treated unstable angina, patients with a myocardial lactate production (MLP) of greater than 15 percent showed an in-hospital mortality rate of 21.4 percent; no deaths were observed in those with less than 15 percent MLP (p < 0.05). Similarly, in patients with acute myocardial infarction, greater than 15 percent MLP identified a high-risk subset (33.3 percent mortality >15 percent MLP versus 0 percent mortality <15 percent MLP, p < 0.05). Without benefit of subgrouping by myocardial lactate analysis, the results of surgical treatment in patients considered candidates for emergency myocardial revascularization were not significantly different from those in patients treated medically. However, surgery favorably altered mortality (11.5 percent surgical mortality versus 26.9 percent medical mortality, p < 0.05) in those patients identified by a greater than 15 percent MLP response to coronary sinus pacing. Hence, among presumably high-risk coronary patients treated medically, myocardial lactate analysis was useful in predicting clinical outcome. In addition, myocardial lactate analysis provided a basis for selection of a subset of patients with acute coronary disease in whom emergency myocardial revascularization was of definite value.

Accuracy of numerical coronary profile. Correlation of risk factors with arteriographically documented severity of atherosclerosis.

We compared a coronary risk profile (developed by the Framingham Study) based on age, sex, cigarette smoking, glucose intolerance, left ventricular hypertrophy, systolic blood pressure and serum cholesterol to angiographically determined severity of coronary-artery disease in 158 consecutive patients undergoing cardiac catheterization. A profile of 1.0 indicated average relative risk. Risk profiles for 105 patients with angiographically documented coronary-artery disease was 1.52 whereas it was 1.08 for the group without coronary disease (P less than 0.01). There was no difference between the patients with coronary disease with (1.44) and those without previous infarct (1.46). The coronary risk profile, however, increased with increasing severity of coronary disease. The high-risk coronary patient can be identified by seven easily measured risk factors, and the extent of coronary-artery disease increases with the number and severity coronary risk factors.

Home-monitoring of high-risk coronary patients

Home-monitoring of high-risk coronary patients

Prehospital care of acute myocardial infarction.

It has been estimated recently that half of deaths among the patients with acute myocardial infarction occur before they ever reach the hospital for definitive medical care. One of the major reasons for the high incidence of death was attributed to delays in reaching medical care, involving patients themselves, physicians, transportation, and receiving areas of the hospital. In order to reduce this high mortality substantially we should focus our attention on the prehospital care of this disease, which may include several major approaches. A. To shorten the delay in securing medical care: 1. Public education, with emphasis on the early warning symptoms and signs of acute myocardial infarction, and the need and importance of seeking early medical care, with special attention directed toward the high-risk coronary patients. 2. Professional education. 3. Mechanisms to direct and/or bring patients with suspected or proven acute myocardial infarction promptly to the system of medical care with special emphasis on the utilization of a telephone information center and provision of rapid transportation. B. Establishment of emergency life-support stations for screening, monitoring, and early stabilization of cardiac arrhythmias: 1. Fixed. a. Emergency department of hospitals, preferably with an attached precoronary care area. b. Areas where many employees are working on weekdays. c. Areas where many people move in and out from day to day. d. Areas where there is periodic concentration of mass population. 2. Mobile. a. Mobile coronary care unit. b. Mobile intensive care unit. C. Prevention of sudden death: 1. Study of mechanism and clinical environment of sudden death. 2. Development of techniques for early diagnosis and management of acute myocardial infarction prior to inception of symptoms. 3. Identification of individuals prone to sudden death. 4. Preventive measures directed toward the individuals prone to sudden death. a. Effective control of risk factors. b. Intermittent or periodic electrocardiographic monitoring in these individuals. c. Long-term antiarrhythmic therapy for these individuals. d. Possibility of implanting an automatic defibrillator in patients with previous myocardial infarction or in those recovered from ventricular fibrillation. 5. Early administration of antiarrhythmic drugs in patients with suspected or proven acute myocardial infarction.